ClinVar Miner

Submissions for variant NM_005236.3(ERCC4):c.2178C>T (p.Arg726=)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV001121238 SCV001279807 uncertain significance Xeroderma pigmentosum, group F 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001312489 SCV001502945 uncertain significance Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia, complementation group Q 2020-10-07 criteria provided, single submitter clinical testing This sequence change affects codon 726 of the ERCC4 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ERCC4 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ERCC4-related conditions. ClinVar contains an entry for this variant (Variation ID: 888106). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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